Introducing Systemic Therapy in Advanced DTC

In this segment, Dr. Greg Randolph explores when and how systemic therapy is introduced for patients with progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). He notes that not all structural disease requires immediate systemic treatment, low-volume, radiographically stable metastases can often be safely observed. Systemic therapy becomes relevant when there is clearly progressive, RAI-refractory disease documented on imaging.

Dr. Randolph highlights redifferentiation therapy as an important emerging strategy. Using next-generation sequencing to define the tumor’s driver mutation, clinicians may deploy targeted inhibitors to “reset” tumor biology, restoring sodium iodide symporter function and RAI uptake. This can allow patients to receive additional RAI with potentially improved efficacy.

If disease continues to progress despite RAI and redifferentiation efforts, tyrosine kinase inhibitor (TKI) therapy is considered. Decisions around initiating TKIs incorporate radiographic progression, symptom burden, disease distribution, and patient fitness, aiming to balance therapeutic benefit with toxicity in advanced DTC.